The association between early onset of alcohol, smokeless tobacco and marijuana use with adult binge drinking in United States

Binge drinking is a deadly pattern of excessive alcohol use that is associated with multiple diseases in the United States. To date, little is known about the associations between the early onset of substance use and other factors with the severity of adult binge drinking. The 2018 National Survey on Drug Use and Health data was used to identify binge drinking (binary and in number of days in the past month). Age at onset was categorized into four groups as 1–12, 13–14, 15–17, or beyond 18. Weighted multivariate logistic regression and Poisson regression analyses were performed to examine the associations between early onset of alcohol, smokeless tobacco, and marijuana use with binge drinking. The severity of binge drinking was statistically significantly associated with substance use (4.15 days in a month), early onset of alcohol, smokeless tobacco, and marijuana use (2.15–4.93 days, all p-values < 0.0001), after accounting for the covariates. Past year substance use disorder is strongly associated with binge drinking. The severity of adult binge drinking is significantly associated with early onset of substance use including alcohol, smokeless tobacco, and marijuana. Continued efforts are warranted to improve substance use prevention and treatment tailored for adolescents and youths to prevent development of adult binge drinking.


Measures. Dependent variables include binge drinking as a dichotomized variable as well as an ordinal
variable. Participants were asked if they engaged in alcohol use and binge drinking in the past month. Binge Alcohol Frequency, IRALCBNG30D, is defined as the number of days (ranged 0 to 30 days) in the past month on which the respondent reported drinking five or more drinks on the same occasion for males or four or more drinks on the same occasion for females. For this variable, "occasion" means at the same time or within a couple hours of each other. Predictors were selected based on an association with binge drinking reported by previous literatures.
Demographic variables. Demographic factors included participants' age in groups (18)(19)(20)(21)(22)(23)(24)(25) years, 26-49 years, 50-64 years and 65 years or older), sex (male and female), and race/ethnicity (Non-Hispanic White, Non-Hispanic African Americans, Hispanics, and others). The annual income was dichotomized into lower than $49,999 and $50,000 or more. Insurance status was defined to be "Yes" if a person was cover by any of the following insurances: (1) private insurance, (2)  Substance use disorders (SUDs) in the past year. NSDUH defined SUDs as a combined variable of abuse or dependence on illicit drugs in the past year, if the respondent reported a positive response to three or more of the following seven dependence criteria, derived from the criteria in the American Psychiatric Association (APA) Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) 29 : 1. spent a great deal of time over a period of a month getting, using, or getting over the effects of the substance; 2. unable to keep set limits on substance use or used more often than intended; 3. needed to use substance more than before to get desired effects or noticed that using the same amount had less effect than before; 4. unable to cut down or stop using the substance every time he or she tried or wanted to; 5. continued to use substance even though it was causing problems with emotions, nerves, mental health, or physical problems; 6. reduced or gave up participation in important activities due to substance use; 7. if they had experienced substance specific withdrawal symptoms at one time that lasted for longer than a day after they cut back or stopped using. Illicit drug abuse or drug dependence is defined as abusing any of the following substances: marijuana, hallucinogens, inhalants, tranquilizers, cocaine, heroin, pain relievers, stimulants, or sedatives.
Serious psychological distress (SPD). SPD is a nonspecific measure of psychological distress that has been psychometrically validated and shown to be able to discriminate community DSM-IV cases from non-cases 30 . It is intended to characterize having at least 1 mental disorder, such as major depressive disorder, generalized anxiety disorder, or schizophrenia, as well as having serious impairment of body function. SPD was determined using the Kessler 6 (K6) scale, which comprised 6 questions asking how often during the past 30 days a person felt "so sad that nothing could cheer them up, " "nervous, " "restless, " "hopeless, " "worthless, " or that "everything was an effort. " Responses were scored from 0 (none of time) to 4 (all the time) for each question and summed to produce a total score (0 to 24) of the 6 questions. A score of 13 or above was employed to define SPD 30 .
Multiple chronic conditions. Many chronic conditions including asthma 8 , cancer 3,4 , chronic obstructive pulmonary disease (COPD) 9 , diabetes 10 , kidney diseases 11 , heart conditions and hypertension 7 had well-established associations with binge drinking. The aforementioned chronic conditions in the lifetime were dichotomized into "yes" or "no". Subjects were considered to have these conditions if they responded "yes" to the questions that either a doctor or other medical professional told they had such conditions in the lifetime. Multiple chronic www.nature.com/scientificreports/ conditions were created by counting the number of such conditions and the indicator was coded as none, one, two or more.
Early onset substance use prior to age 18. This study included ages at the first use of alcohol, smokeless tobacco, and marijuana, respectively. Three variables were further categorized into four age groups: 1-12, 13-14, 15-17, and 18 or more. The NSDUH data is rich in various substance use including alcohol, tobacco, marijuana, prescription pain reliever, methamphetamine, cocaine, etc 29 . However, many of them have high correlations and cannot be modelled together due to multi-collinearity. In this study, we selected the three most frequently involved substance uses with binge drinking as the objective of early onset of substance use.

Statistical analysis.
We weighted all analyses to account for the complex survey design. All analyses were conducted using SAS 9.4 (SAS Institute, Cary, North Carolina, USA). The statistical significance level was set at 0.05.
Descriptive statistics and prevalence. We first calculated descriptive statistics to estimate the weighted prevalence of binge drinking, overall and by each category of covariate. The SAS PROC SURVEYFREQ was used for weighted estimation of prevalence and Chi-square test was used to compare the prevalence of binge drinking across demographic subgroups (age, gender, and race), socioeconomic factors (income level, health condition, and health insurance status), clinical factors (multiple chronic disease and SPD), and substance use associated factors (SUD, early onset of alcohol use, early onset of smokeless tobacco use, and early onset of marijuana use).
We also calculated the weighted mean number of days of binge drinking in the past month across the subgroups through SAS PROC SURVEYMEANS.
Multivariate logistic regression analysis. The PROC SURVEYLOGISTIC was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between factors and binge drinking. Two models were conducted in sequence following a purposeful model selection process 31 . In model I, bivariate logistic model was fitted for each aforementioned factor to assess its association with binge drinking. In model II, the weighted multivariate logistic regression was fitted to adjust for potential factors with p-value significant at 0.2 in the model one 32 . Adjusted odds ratios (aORs) and 95% CIs were reported for the selected factors in model II.
Poisson regression analysis. The PROC GLIMMIX was employed to fit a Poisson regression model to estimate the coefficients of aforementioned factors for the number of days of binge drinking in the past month 33 . This approach addressed the limitation of unable to account for sampling weight by traditional procedures of GEN-MOD and COUNTREG in Poisson regression. Regression coefficient (β) and corresponding standard error (SE), t-value and p-value were reported. Although zero-inflated Poisson regression seemed to be a better fit for this analysis, given that many people reported no binge drinking in the past month ( Fig. 1), the SAS 9.4 cannot take both zero-inflated distribution and complicate survey weight into account at the same time. Thus, a Poisson regression model was fitted by PROC GLIMMIX.
Institutional review board statement. The is a secondary data analysis which was exempt for review by the West Virginia University Institutional Review Board. Participants' consents are not applicable in this study.

Results
Prevalence of binge drinking. The prevalence of binge drinking in the past year is listed in Table 1 Weighted Poisson regression analyses of number of days of binge drinking. The estimated model effects (β, SE, t, p) of multivariable Poisson regression are also presented in Table 2. Almost all factors other than age were statistically associated with the frequency of binge drinking as a count outcome. The coefficient β indicates an average change in the number of days of binge drinking in the past month associated with 1 unit change of that factor. For example, the largest β of 0.60 was associated with early alcohol use before age 12, which means that on average, people who initiated alcohol use before 12 had 0.6 more day of binge drinking in a month, compared to those who had no early initiation of alcohol. Other large βs were found in the early onset of alcohol use in

Discussion
The current study confirms how early onset of substance use affects the development of adult binge drinking behavior and expands our understanding by quantifying the impact of early onset of substance use on the severity of binge drinking. All three predictors of onset of substance use prior to age 18, including alcohol, smokeless tobacco, and marijuana, were identified as independent predictors of binge drinking and were found statistically significantly associated with the binge drinking to various extents. Early onset of alcohol use was the strongest, following smokeless tobacco and marijuana use. The current study aligns with previous findings that the earlier onset of alcohol drinking, the more likely these individuals are to develop binge drinking and other alcohol use related problems 16,34 . However, some previous studies had contradicted findings. Moss et al. 35 found a positive association between early marijuana use and later binge drinking, but a surprisingly negative effect of early  www.nature.com/scientificreports/ on how different patterns or sequences of early onset of substance use (e.g., initiation of alcohol use leads to tobacco use and then marijuana use) affect binge drinking may shed light on this question. Of great importance, the current study supports that the presence of SUD diagnosis in the past year is one of the strongest predictors of binge drinking. On average people who were diagnosed with SUD last year had over two times more days of binge drinking in a month, compared to people without SUDs (4.15 vs. 1.95 days). Previous studies have shown that adolescent use of all the three substances was strongly associated with SUD diagnoses in the young adulthood 13,[36][37][38][39][40] . The significant impact of SUD on binge drinking might be an additive or synthetic effect of the onset of experimenting with substances at an early age 35 . Thus, delaying the onset of substance use, including tobacco, alcohol, marijuana, would be an effective strategy for preventing both addiction and binge drinking in adulthood life.
Socio-economic factors are mostly marginally statistically (p-values in 0.05-0.20) associated with binge drinking, including low house income (< $49,999), relatively good health (excellent or very good), and no health Table 2. Multivariable logistic regression with binge drinking as binary and Poisson regression with number of days of binge drinking in the past month as a count variable. ref reference group, AA African American, aOR adjusted odds ratio, CI confidence interval, β regression coefficient, SE standard error, SUD substance use disorder, SPD serious psychological distress. www.nature.com/scientificreports/ insurance. These findings are not greatly contradicting with previous studies 28,42 . Alcohol consumption is wellknown to be causally associated with and complicated with many chronic diseases including diabetes, heart diseases, and injuries [7][8][9][10][11] . However, the present study surprisingly found that higher number of chronic diseases was a protective factor of binge drinking, which aligns with a previous finding that the prevalence of binge drinking was lower among older adults with two or more chronic diseases 28 . The reason for this seemingly unjustified finding might be that patients in multiple chronic diseases are in serious health conditions and have to follow doctor's orders to avoid alcohol consumption 28 . Strengths. The analysis provides a unique strength that measures the severity of binge drinking by number of days in the past month as a count outcome. To our knowledge, the study is the first to investigate risk factors associated with binge drinking as a count outcome using a weighted Poisson regression model in a nationally representative sample. Another unique strength of the current study exists in the classification of age at onset of substance use, the findings of which indicate that the influential range of age at early onset varies by substance. Onset of alcohol use at any age prior to 18 was found statistically significantly associated with the binge drinking (all ORs > 2); onset of smokeless tobacco use after 13 and onset of marijuana use at any age before 18 were also found statistically significantly related to the binge drinking (all ORs ranging from 1 to 2).
Limitations. Despite of many strengths that have shown in this section, our study presents a series of limitations. The cross-sectional design impedes an interpretation of causational factors. The nature of NSDUH data is prone to recall bias, social desirability bias, and non-differential misclassification bias due to the collection of information on the past behaviors (e.g., past-month binge drinking and number of days of binge drinking in the past month) 20,27 . There is no worldwide consensus of definition of "binge drinking" or "heavy drinking episode". The definition used in this study was derived from the US academia and federal agency 29,43 , and could be different from other reports or publications worldwide. Another noteworthy limitation to the interpretation of our results is that the study failed to take age of first intoxication by alcohol into consideration. While age of onset of alcohol use has been identified as an independent risk factor of binge drinking, previous studies 16,17 suggest that delay to intoxication may be an important determinant of negative alcohol use outcome and should be considered in the modelling. Although the NSDUH includes various substance use information, the study only includes the main three substances which are the most prevalent among binge drinking population. Besides, unfortunately, this study cannot take interpersonal factors, including parental monitoring and relationships between parents and adolescents, as known risk factors into the modelling 44 .

Conclusion
Binge drinking is prevalent among adults and its severity is significantly associated with early onset of substance use to various extents, especially with regards to early alcohol use. The findings from this study could help identify adolescents at high risk of binge drinking before age of 12, especially among those who use dual or multiple products of tobacco, alcohol, and/or marijuana. Reduced alcohol, tobacco, and marijuana use should be integrated in the brief physician advice towards adolescents with drinking problems, any substance use issues, mental health conditions and/or multiple chronic diseases. Health education that specifically emphasize delayed use of alcohol, tobacco, and/or marijuana should be conducted on campus, especially among high school students. The U.S. Preventive Services Task Force recommends alcohol screening for all adults aged at or over 18 years 14 , and it is becoming important to extend the alcohol screening among younger populations. Future research should examine how different patterns of early onset of substance use affect binge drinking while controlling for the onset of substance use.

Data availability
The data that support the findings of this study are publicly available at Substance Abuse & Mental Health Data Archive, the National Survey on Drug Use and Health 2018 data.